Yoshida_1994_Toxicol.Lett_74_167

2-Substituted-4H-1,3,2-benzodioxaphosphorin 2-oxides (2-substituted-BDPOs) are of special interest as neuropathy target esterase (NTE) inhibitors because they include not only the neuropathic metabolite of tri-o-cresyl phosphate (the 2-methylphenoxy analog) but also the most potent NTE inhibitors known. These compounds react much faster with NTE than 2 standard inhibitors, O,O-diisopropyl fluorophosphonate (DFP) and mipafox. alpha-Chymotrypsin is similar to NTE in undergoing rapid inhibition by BDPOs which is known to involve phosphorylation followed by aging. NTE and alpha-chymotrypsin were compared for reaction rates with BDPOs varying in the 2-substituent as follows: 4-methyl-, 4-propyl-, and 4-hexylphenoxy; butyl, octyl and dodecyl; (S)- and (R)-butyl. The active site of NTE differs from that of alpha-chymotrypsin in preference for long-chain substituents and in stereospecificity.